Epoxidations ketone catalysts

Figure 6.4 Mechanism of epoxidation by a chiral ketone catalyst.

Since tetranuclear platinum-blues are oxidized by 02 to Pt(III) dinuclear complexes and are reversively reduced to the platinum-blues and further to the Pt(II) dinuclear complexes, an attempt was made to use these complexes as catalysts for olefin oxidation to ketones and epoxides. The catalysts used were a-pyrrolidonato-bridged Pt-tan [Pt4(NH3)8(C4H6N0)4](N03)6 -2H20 (19), pivalamidato-bridged Pt-blue [Pt4(NH3)8(C5H10NO)4](NO3)5 (57), a-pyrrolidonato-tan [Pt4(NH3)8... 

The breakthrough came already in 1996, one year after Curd s prediction, when Yang and coworkers reported the C2-symmetric binaphthalene-derived ketone catalyst 6, with which ee values of up to 87% were achieved. A few months later, Shi and coworkers reported the fructose-derived ketone 7, which is to date still one of the best and most widely employed chiral ketone catalysts for the asymmetric epoxidation of nonactivated alkenes. Routinely, epoxide products with ee values of over 90% may be obtained for trans- and trisubstituted alkenes. Later on, a catalytic version of this oxygen-transfer reaction was developed by increasing the pH value of the buffer. The shortcoming of such fructose-based dioxirane precursors is that they are prone to undergo oxidative decomposition, which curtails their catalytic activity. 

These encouraging results have led to a surge of activity in this promising area, such that numerous ketone catalysts have been developed for asymmetric epoxidations. A... 

Other advantages include a mechanism that allows one to rationalize and predict the stereochemical outcome for various olefin systems with a reasonable level of confidence utilising a postulated spiro transition state model. The epoxidation conditions are mild and environmentally friendly with an easy workup whereby, in some cases, the epoxide can be obtained by simple extraction of the reaction mixture with hexane, leaving the ketone catalyst in the aqueous phase. 

Chiral dioxiranes, generated in situ from chiral ketones and Oxone , are promising reagents for the asymmetric epoxidation of unfunctionalized alkenes. Chiral ketone catalysts that are easily accessible in both enantiomers are targets for development. 

AN OXAZOLIDINONE KETONE CATALYST FOR THE ASYMMETRIC EPOXIDATION OF cis-OLEFINS... 

Because the petrochemical industry is based on hydrocarbons, especially alkenes, the selective oxidation of hydrocarbons to produce organic oxygenates occupies about 20% of total sales of current chemical industries. This is the second largest market after polymerization, which occupies about a 45% share. Selectively oxidized products, such as epoxides, ketones, aldehydes, alcohols and acids, are widely used to produce plastics, detergents, paints, cosmetics, and so on. Since it was found that supported Au catalysts can effectively catalyze gas-phase propylene epoxidation [121], the catalytic performance of Au catalysts in various selective oxidation reactions has been investigated extensively. In this section we focus mainly on the gas-phase selective oxidation of organic compounds. 

H. Q. Tian, X. G. She, and Y. Shi, Electronic probing of ketone catalysts for asymmetric epoxidation. Search for more robust catalysis, Org. Lett. 2001, 3, 715-718. 

Many other variations of the basic structure 10 have been explored, including an-hydro sugars and carbocyclic analogs, the latter derived from quinic acid 13 [23-26]. In summary, the preparation of these materials (e.g. 14-16) requires more synthetic effort than the fructose-derived ketone 10. Occasionally, e.g. when using 14, catalyst loadings can be reduced to 5% relative to the substrate olefin, and epoxide yields and selectivity remain comparable with those obtained by use of the fructose-derived ketone 10. Alternative ex-chiral pool ketone catalysts were reported by Adam et al. The ketones 17 and 18 are derived from D-mannitol and tartaric acid, respectively [27]. Enantiomeric excesses up to 81% were achieved in the epox-idation of l,2-(E)-disubstituted and trisubstituted olefins. 

Chiral ketone catalysts of the Yang-type (5a and 5b, see above) and of the Shi-type (10, Scheme 10.2) have been successfully used for kinetic resolution of several racemic olefins, in particular allylic ethers (Scheme 10.4) [28, 29]. Remarkable and synthetically quite useful S values of up to 100 (ketone 5b) and above 100 (ketone 10) were achieved. Epoxidation of the substrates shown in Scheme 10.4 proceeds with good diastereoselectivity. For the cyclic substrates investigated with ketone 10 the trans-epoxides are formed predominantly and cis/trans-ratios were usually better than 20 1 [29]. For the linear substrates shown in Scheme 10.4 epoxidation catalyzed by ketone 5b resulted in the predominant formation of the erythro-epoxides (erythro/threo-ratio usually better than 49 1) [28]. 

Cavallo et al. from (+)-dihydrocarvone and evaluated in the asymmetric epoxida-tion of several silyl enol ethers [32]. Enantiomeric excess up to 74% was achieved in the epoxidation of the TBDMS trans-enol ether of desoxybenzoin with the fluoro ketone 19d (30 mol% of the ketone catalysts). In earlier work Solladie-Cavallo et al. had shown that the fluoro ketones 19a and 19e can be used to epoxidize trans-stilbene with up to 90% ee (30 mol% ketone catalyst) [33], Asymmetric epoxidation of trans-methyl 4-para-methoxycinnamate using ketone 19e as catalyst is discussed in Section 10.2. 

In the course of their exploration of structure-activity relationships for ketone catalysts, Denmark et al. noted that oxoammonium salts such as 29-33 are very efficient catalysts of the epoxidation of olefins [34a]. Unfortunately, enantiomeric excesses achieved with this class of ketone catalyst have not yet exceeded 40% (30, epoxidation of tram-fl-rn eth yI styrene . With the fhiorinated oxoammonium catalyst 23 already mentioned, however, 58% ee was achieved in the asymmetric epoxidation of trans-stilbene [34b]. 

During our further studies of ketone catalysts, ketone 16 was found to be highly enantioselective for a number of acyclic and cyclic d.s-olefins (Table 10.6).73-74 It is important to note that the epoxidation is stereospecific with no isomerization observed in the epoxidation of acyclic systems. Ketone 16 also provides encouragingly high ee s for certain terminal olefins, particularly styrenes.74-75 In general, ketones 1 and 16 have complementary substrate scopes. In our subsequent study of the conformational and electronic effects of ketone catalysts on epoxidation, ketone 17, a carbocyclic analog of 16, was found to be highly enantioselective for various styrenes (Table 10.7).76... 

A further series of ketone catalysts containing spiro ethers and lactones have been examined in the asymmetric epoxidation of phenylcyclohexene (cf Table 5, entry 2 94% yield, 98% ee) (Figure 11). The substituents on the spiro ring appeared to effect enantioselectivity both sterically and electronically <2005T6409>. 

Asymmetric Epoxidation of Electron-deficient trans-Olefins. (f )-l can also catalyze epoxidation of electron-deficient trans -olefins, especially ( )-cinnamate derivatives (eq 4). With 5 mol % of (f )-l, epoxidation of acrylate (5) is completed in 27 h with 74% yield and 85% ee. The crude product can be purified using a continuous dissolution and crystallization process to afford enantiomerically pure product and recover the ketone catalyst simultaneously. A similar practical method has been employed for large-scale synthesis of a key intermediate for diltiazem hydrochloride (a potent calcium antagonist for treatment of cardiovascular disease). 

SYNTHESIS OF l,2 4,5-DI-0-ISOPROPYLIDENE-D-erythro-2,3-HEXODIULO-2,6-PYRANOSE. A HIGHLY ENANTIOSELECTIVE KETONE CATALYST FOR EPOXIDATION... 

Catalysts based on palladium, such as 10% palladium on charcoal, have also been used frequently. In these cases ketones derived from isomerization of the epoxides are often obtained as by-products. As shown in Table 11, both product- and regio-selectivities are highly dependent on the configuration of the starting epoxides. Geneste et suggested that the selectivity may be controlled at the stage of the approach of epoxides to catalyst. 

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